Down syndrome has many features. Duodenal atresia is one of them that you must not forget.

Double bubble sign indicates duodenal atresia, link these 3 terms closely: Double bubble sign > Duodenal atresia > Down’s syndrome is easy to remember as they all start with the letter “D”.

Down’s Syndrome :

Clinical features: Up slanting palpebral fissures, epicanthic folds, protruding tongue, small ears, round/flat face- flat occiput, Single palmar crease, pronounced 'sandal gap' between the big and first toe

Congenital heart defects, duodenal atresia, Hirschsprung's disease

Cardiac complications- Atrioventricular septal canal defects, ventricular septal defects

Later complications- Subfertility, learning difficulties, short stature, acute lymphoblastic leukemia, Alzheimer's.

The guidelines advise that women with a family history (first-degree or second-degree relative) that appears to increase their risk of developing ovarian cancer should be referred to a clinical genetics service for full assessment of risk.

Genetic counseling would be more appropriate here compared to a CA-125 as she has no symptoms of ovarian cancer and a pelvic ultrasound scan was seen to be normal.

Any of the following criteria would signify an increased risk for ovarian cancer :

• The woman is a known carrier of the BRCA1 or BRCA2 cancer gene mutations

• She has a first-degree or second-degree relative who carries a gene mutation

• Two family members who are first-degree relatives of each other have ovarian cancer

• One family member has both breast and ovarian cancer.

These high-risk women should be offered genetic screening and counseling.

Steps to investigate a patient with suspected ovarian cancer:

1. CA 125 test 

2. Pelvic and abdominal ultrasound scans

3. CT scan of the pelvis and abdomen

4. MRI scan can be used for pre-operative staging

5. High-risk women may be offered referral for prophylactic salpingo-oophorectomy.

Unfortunately, this is not the type of question that you figure out using logic. You need to know that Congenital Adrenal Hyperplasia is an autosomal recessive genetic disorder. This means that for a child to have the condition, both parents need to have the recessive gene.

This would result in 25% of offspring being normal, 50% of offspring being carriers, and 25% of offspring having the disease in its active form.

CONGENITAL ADRENAL HYPERPLASIA :

• Autosomal recessive disorder

• Comes in three forms: 21-hydroxylase, 11-hydroxylase, or 3-? hydroxysteroid dehydrogenase deficiency

• Females with classic form: ambiguous genitalia

• Males with classic form: hyperpigmentation, penile enlargement, aldosterone deficiency

• Males with salt-losing form: typically present at 7-14 days of life with vomiting, weight loss, lethargy, dehydration, hyponatremia, and hyperkalemia. It is unlikely you would be asked how to treat this disease for the exam. Just know how to identify the various presentations, and remember that it is an autosomal recessive disorder.

21-hydroxylase deficiency : The most common and is characterized by cortisol deficiency (with or without aldosterone deficiency) and androgen excess.

11-beta-hydroxylase deficiency : The second most common and is characterized by aldosterone deficiency which causes salt-wasting in early infancy.

Ehlers-Danlos syndrome : There are many types of EDS based on different gene mutations affecting the structure or assembly of different collagens. Many syndromes overlap and it may be difficult to differentiate one from the other.

But not, however, they all share common features:

- Hyperelasticity of skin

- Joint hypermobility

Those are the only two signs you need to know for your exam for Ehlers-Danlos syndrome.

The key to answering this question is to look for associations. Cerebral aneurysms are recognized as associated with polycystic kidney disease. Since polycystic kidney disease has a genetic component, it is safe to assume that the question writers are trying to hint that the brother also has polycystic kidney disease.

The most serious possible complication of polycystic kidney disease is a cerebral aneurysm that ruptures. This causes a subarachnoid haemorrhage.

Cystic fibrosis (CF) is an autosomal recessive disorder. This means that the parents of the cystic fibrosis child are carriers. If a child is born to parents who carry the same autosomal recessive change (mutation), the child has a 1 in 4 chance of inheriting the abnormal gene from both parents and developing the disease.

The child would have a 50% (1 in 2) chance of inheriting one abnormal gene.

This would make him/her a carrier. Autosomal recessive.

The child has a 25% chance of inheriting the genetic condition if BOTH parents are carriers of the faulty gene.

• Cystic fibrosis

• Sickle cell anaemia

• Thalassaemia - Autosomal dominant : The child has a 50% chance of inheriting the genetic condition if ONE parent has the mutation.

• Huntington

• Neurofibromatosis

• Autosomal dominant polycystic kidney disease : X-linked dominant. The child has a 50% chance of inheriting the genetic condition if the MOTHER has the mutation (the MOTHER would also be affected by the disorder). A female child has a 100% chance of inheriting the genetic condition and a male child has a 0% chance of inheriting the genetic condition if the FATHER has the mutation (the FATHER would be affected by the disorder).

• Fragile X syndrome : If you google image Fragile X syndrome, you would realize that all the pictures are of male children. Why are the features of Fragile X-syndrome seen more in males even though females are more often affected (an X-linked dominant condition)?

This is because males display a complete penetrance and therefore almost always display symptoms of Fragile X syndrome however females display penetrance of about 50% as a result of having a second normal X-chromosome so they have symptoms that are less severe than males.

Most women with Turner syndrome have normal intelligence however some do still have learning difficulties, especially involving spatial visualization that may be needed for mathematics. They also may have issues with nonverbal and social skills.

Human growth hormone injections during childhood are used as part of the treatment of Turner syndrome girls to increase height to an average adult height. Oestrogen replacement therapy is also used to promote the development of breasts and hips and to prevent osteoporosis and it is used in childhood.

Advanced maternal age is not a risk factor for Turner syndrome. Almost all affected women are infertile due to ovarian dysgenesis, but some can conceive with assisted reproduction.

AMENORRHOEA : Amenorrhoea is the absence of menstruation.

Pathological amenorrhoea is the failure to menstruate for at least 6 months. Amenorrhoea can be divided into -

• Primary amenorrhoea – Lack of menstruation before age 16 years or 14 in the absence of secondary characteristics

• Secondary amenorrhoea – Cessation of menstrual cycles following established cycles 

• Hypothalamic amenorrhoea. Most common. Usually due to low BMI or excessive exercise

• Polycystic ovarian syndrome (PCOS)

• Hyperprolactinaemia

• Premature ovarian failure - Raised FSH levels.

• Anatomical problems - Usually results in primary amenorrhoea. Vaginal examinations to rule out imperforate hymen is important.

 Pelvic ultrasound is also useful to determine the pelvic anatomy (Mullerian agenesis). 

Anatomical problems can also cause secondary amenorrhoea (Asherman’s syndrome)

• Thyroid problems - Both hyperthyroidism and hypothyroidism can cause amenorrhoea.

Don’t forget pregnancy as a cause of amenorrhoea.

Specifics to look for in the stems

• Short stature – May indicate Turner syndrome

• Hirsutism, acne (androgen excess) – May indicate PCOS or hyperprolactinemia

• Menopausal symptoms in women before age 40 – May indicate premature ovarian failure

• Eating disorder – May indicate anorexia nervosa

• Galactorrhoea – May indicate hyperprolactinemia.

The most appropriate test at this gestation would be an amniocentesis.

Amniocentesis is an invasive, diagnostic antenatal test. It involves taking a sample of amniotic fluid to examine fetal cells found in this fluid. Amniocentesis is an invasive procedure, diagnostic antenatal test involving taking a 20ml sample of amniotic fluid using a transabdominal needle under ultrasound guidance to examine fetal cells found in this fluid.

It is offered after screening tests have indicated a high risk of fetal abnormality or in women considered to be at high risk, for example, if above 35 years old. Amniocentesis is usually performed at 16 weeks and the risk of fetal loss is 0.5-1%.

Conditions which may be diagnosed :

- Neural tube defects (raised AFP levels in the amniotic fluid)

- Chromosomal disorders

- Inborn errors of metabolism

Timing of amniocentesis : Mid-trimester (between 15 and 18 weeks of gestation):  This is the most common time for the procedure.

Sweat testing can confirm the diagnosis of cystic fibrosis and is 98% sensitive. The rectal prolapse is due to bulky stools which is seen in cystic fibrosis.

The likely diagnosis is Klinefelter’s syndrome. While it is true that serum testosterone is low or low normal and FSH and LH are elevated (FSH >LH) in Klinefelter’s syndrome, the diagnosis is confirmed by chromosomal analysis. Raised LH and FSH are due to a lack of negative feedback from low levels of circulating testosterone in the pituitary gland.

The most common indications for karyotyping are hypogonadism and infertility. Many with known Klinefelter's syndrome are not diagnosed until they are adults. The single best test that confirms diagnosis is a chromosomal analysis.

Klinefelter’s syndrome (XXY) Findings :

- Mental retardation (average IQ 85-90)

- Behavioral problems

- Long limbs ( decreased upper: lower segment ratio)

- Tall and slim

- Hypogonadism

- Infertility

- Gynecomastia

This lady has neurofibromatosis. The risk of an affected individual with neurofibromatosis type 1 or 2 transmitting the disease to their child is 50% Neurofibromatosis There are two types of neurofibromatosis, NF1 and NF2. Both are inherited in an autosomal dominant fashion.

Type 1: More common form

• Café-au-lait spots

axillary/groin freckles

• Peripheral neurofibromas

• Iris hamartomas (Lisch nodules)

• Scoliosis

• Association with phaeochromocytomas

Type 2: A central form with CNS tumors rather than skin lesions

• Bilateral acoustic neuromas

• Multiple intracranial schwannomas, meningiomas and ependymomas.

Duchenne muscular dystrophy is an X-linked recessive condition that presents in early childhood and inevitably progresses. Some carriers also have symptoms. New mutations are common in DMD; this means that female relatives of a child with DMD are not necessarily carriers of the gene. Becker's muscular dystrophy (BMD) is similar to the more common muscular dystrophy- Duchenne muscular dystrophy (DMD) - but the clinical course is milder.

As with DMD, there is muscle wasting and weakness which is mainly proximal. Generally, walking difficulties begin after the age of 16 in Becker's muscular dystrophy. Thus the most appropriate answer here is Duchenne’s muscular dystrophy. Duchenne muscular dystrophy, can’t hold objects - Inability to run - waddling gait when attempting to do so.

- Gower’s sign, proximal muscle weakness - +/- Respiratory or cardiac signs/symptoms - Elevated creatine kinase, AST, ALT Diagnosis: - Creatine kinase - initial  (CK levels are very high (10-100 x normal from birth).

- Blood sample and muscle biopsy. genetic testing for dystrophin mutations. PCR - Neuromuscular assessment diagnosis severity and determine management - Genetic testing after a positive biopsy diagnosis of DMD is mandatory.

The right-handed involuntary writhing movements are called chorea. These are uncontrollable limb movements. Cognitive abilities are progressively impaired in Huntington’s which explains the memory loss, poor concentration, and the inability to recognize household objects. A general lack of coordination and an unsteady gait often follow. The final clue is the strong family history.

Huntington’s disease is an autosomal dominant disorder.

One can imagine either her father or mother with this disorder. Huntington’s disease - Huntington's disease (HD) is an autosomal-dominant, progressive neurodegenerative disorder with a distinct phenotype Presentation - Typically, onset of symptoms at middle age - Early signs may be personality change, self-neglect, and clumsiness - Incoordination - Cognitive decline - Behavioural difficulties - Later Chorea, dystonia, rigidity, and dementia.

Duchenne muscular dystrophy X-linked recessive condition which presents in early childhood and inevitably progresses. Some carriers also have symptoms. New mutations are common in DMD; this means that female relatives of a child with DMD are not necessarily carriers of the gene. Presentation:

• Classic presentation is a boy coming into the clinic by age 4-8 years

• Delayed motor milestone:  walking at > 18 months, can’t hold objects  Inability to run - waddling gait when attempting to do so.

• Gower’s sign, proximal muscle weakness +/- Respiratory or cardiac signs/symptoms

• Elevated creatine kinase, AST, ALT Diagnosis: - Creatine kinase - initial  (CK levels are very high (10-100 x normal from birth). - Blood sample and muscle biopsy genetic testing for dystrophin mutations PCR - Genetic testing after a positive biopsy diagnosis of DMD is mandatory Becker’s muscular dystrophy (BMD)

• is similar to the more common muscular dystrophy – Duchenne muscular dystrophy (DMD) – but the clinical course is milder.

• As with DMD, there is muscle wasting and weakness which is mainly proximal.

• Generally, walking difficulties begin after the age of 16 in Becker’s muscular dystrophy.

Pay special attention to the final line of the question. In this question, they are specifically asking for chances that this boy is a carrier (not an affected child with cystic fibrosis).

In other stems and questions, they may ask for the chance that this boy will have the disease. Both parents here would have to be carriers to produce a child with cystic fibrosis as it is an autosomal recessive disease.

Therefore, the chances of having: - An unaffected child is 1:4 - An unaffected ‘carrier’ child is 1:2 - An affected child is 1:4

Duchenne muscular dystrophy is an X-linked recessive disorder. Since the first child is affected, it means that the mother is a carrier. Since the sex of the second child is known and noted to be male, the chances of the child being affected are 50%. Other notable X-linked recessive disorders are • Haemophilia A and B • Red-green colorblindness.

Primary amenorrhoea, short stature, low set of ears, and a broad chest with widely spaced nipples are features of Turner syndrome Down’s syndrome and Fragile X syndrome do not present with primary amenorrhoea. Klinefelter’s syndrome affects males. This girl would likely need oestrogen replacement therapy to help the development of her secondary characteristics and help her menstruate spontaneously.

This is a classic presentation of Duchenne muscular dystrophy. The stem would usually present with a preschool boy and a history of abnormal gait. Clues: “rising from a sitting position” (Gower’s sign), hypertrophic calf muscles, and elevated creatine kinase.

The presentation of Becker’s has an onset of around 10 years old or presenting with a young man who is unable to walk. Myotonic muscular dystrophy presents at birth with multi-system complications as with spinal muscular atrophy

type 1.

With option E, symptoms would be similar to Duchenne’s but the proximal muscle weakness would improve with exercise and usually is associated with a tumour of the lung.

This woman is not yet pregnant but planning for pregnancy. The earliest possible diagnostic test for cystic fibrosis is a pre-implantation genetic diagnosis (PGD).

Preimplantation genetic diagnosis (PGD) is a procedure used before implantation to help identify genetic defects within embryos created through in vitro fertilization to prevent certain diseases or disorders from being passed on to the child.

The process helps potential parents prevent the birth of a child with a serious genetic condition. Specialists occasionally recommend these tests if a woman has a family history of a serious genetic condition (e.g. cystic fibrosis).

This patient has Duchenne’s muscular dystrophy. This is an X-linked recessive condition which means it only affects males. The mutation causes faulty coding of the dystrophin protein which is found in muscle fiber membranes therefore, the correct answer is that the lesion is located in the striated muscle.

Prader-Willi syndrome rare congenital disorder characterized by learning difficulties, growth abnormalities, and obsessive eating, caused mostly by deletion of the paternally inherited chromosomal 15q11.2-q13 region.

Prader-Willi syndrome (PWS)

• The striking feature of PWS is massive hyperphagia with associated compulsive food-seeking and consequently marked obesity. Clinical features

• Neonates: hypotonia, sleepiness, unresponsiveness, narrow bifrontal diameter, triangular mouth (feeding difficulties and swallowing problems), strabismus, acromicria (shortness of extremities)

• Childhood/adolescence: short stature, hypogenitalism, behavioral disorders (overeating and obesity, self-injurious behavior).

• Associated features: Small hands and feet, cleft palate, almond-shaped eyes, strabismus, clubfoot, scoliosis.

This patient is suffering from Huntington's disease. It is an autosomal dominant disorder with anticipation. The term “anticipation” is a phenomenon whereby as the genetic disorder is passed on to the next generation, the symptoms of the genetic disorder become apparent at an earlier age. This occurs in each generation whereby the symptoms would appear earlier and earlier.

Huntington’s disease - Huntington's disease (HD) is an autosomal-dominant, progressive neurodegenerative disorder with a distinct phenotype Presentation - Typically, the onset of symptoms in middle age - Early signs may be personality change, self-neglect, and clumsiness - Incoordination - Cognitive decline - Behavioural difficulties - Later  Chorea, dystonia, rigidity, and dementia.

This child has recurrent chest infections and malabsorption. Cystic fibrosis should be at the top of the list of differentials. With established disease, finger clubbing is seen. Sweat testing confirms the diagnosis of cystic fibrosis and is 98% sensitive.

A heel prick test (Guthrie’s test) is where a small sample of blood is taken from your baby’s heel when the baby is 7 to 10 days old. This blood is sent to a lab where it is tested for several conditions, one of which is cystic fibrosis. This cannot be used for a 5-year-old child.

To work out the probability of inheritance, you need to know the disease in question. This woman has neurofibromatosis. Neurofibromatosis is an autosomal dominant condition therefore the chances of this woman’s child having the condition is 50% or 1:2. Neurofibromatosis NF is a genetic disorder causing lesions in the skin, nervous system, and skeleton. The neurofibromatoses are autosomal dominant genetic disorders that encompass the rare diseases NF1, NF2, and schwannomatosis

Type 1 is the more common form

Type 2 is a central form with CNS tumours rather than skin lesions

: Schwannomatosis is a recently recognized form of neurofibromatosis, characterized by multiple non-cutaneous schwannomas, which is a histologically benign nerve sheath tumour: UNAFFECTED PARENT (Father) AFFECTED PARENT (Mother). 

Diagnostic criteria for NF1 The diagnostic criteria for NF1 require at least two of seven criteria:

1. At least six café-au-lait spots or hyperpigmented macules

2. Axillary or inguinal freckles.

3. Two or more typical neurofibromas or one plexiform neurofibroma.

4. Optic nerve glioma.

5. Two or more iris hamartomas. They are called Lisch nodules and are seen by slit-lamp examination.

6. Sphenoid dysplasia or typical long-bone abnormalities such as arthrosis.

Many with known Klinefelter's syndrome are not diagnosed until they are adults. The single best test that confirms diagnosis is a chromosomal analysis. In this question, attending a reproductive endocrine clinic and trying to conceive for the last 3 years is a hint telling you about his infertility.

Klinefelter’s syndrome (XXY) Findings - Mental retardation (average IQ 85-90) - Behavioral problems - Long limbs ( decreased upper: lower segment ratio) - Tall and slim - Hypogonadism - Infertility - Gynecomastia

The two most important clinical features of Turner’s syndrome that you must not forget are impaired pubertal growth and ovarian failure.

The baby here has Edwards syndrome also known as trisomy 18. It is seen in the rising maternal age. The prominent calcaneus (also known as rocker bottom feet) is seen in Edwards syndrome. Rocker bottom feet are also seen in Patau syndrome however with the other signs such as microcephaly, micrognathia (small jaw), and a prominent occiput, Edwards syndrome is the likely genetic disorder here.

The majority of Edward syndrome cases are picked up antenatally based on screening by maternal age, serum markers, and sonographic abnormalities such as growth restriction, polyhydramnios, overlapping of fingers, congenital heart defects, and omphalocele.

The most common sonographic markers detected in the late first or early second trimester are increased nuchal translucency thickness and absence or hypoplasia of the nasal bone.

Half of these infants with Edward syndrome do not survive beyond the first week of life. The majority of them do not survive longer than a year.

The key is the B. Sweat test. [Recurrent chest pain from frequent lung infections including pneumonia or bronchitis."Clubbing" of the fingers is a classic feature of Cystic Fibrosis, although not present in many patients. The digestive enzymes are not being produced, food is not adequately digested (malabsorption) and excess fat and protein are lost in the stools, making them bulky, oily, smelly, and difficult to flush away].

The key is A. Haemochromatosis. [Hemochromatosis itself is a cause of hepatocellular carcinoma and is associated with a raised level of ferritin. Serum ferritin levels elevated higher than 200 mcg/L in premenopausal women and 300 mcg/L in men and

postmenopausal women indicate primary iron overload due to hemochromatosis, especially when associated with high transferrin saturation and evidence of liver disease. Ferritin concentration higher than 1000 mcg/L suggests liver damage with fibrosis or cirrhosis].

Ans. The key is B. Chromosomal analysis. [The diagnosis is Klinefelter’s syndrome. (xxy). The points in favour are i) Infertility ii) Tall stature iii) Bilateral gynaecomastia iv) Bilateral small firm testes].

Ans. The key is D. Marfan syndrome. [Cause of severe crushing chest pain may be aortic dissection or angina. The most common cardiac abnormalities in Marfans syndrome are dilatation of the aorta and mitral regurgitation. Other features are tall and thin stature, with long arms, legs, fingers, and toes. They also typically have flexible joints and scoliosis. There may be partial lens dislocation, where the lens is shifted out of its normal position].

Ans. The key is D. Congenital adrenal hyperplasia. [ i) ambiguous genitalia ii) salt wasting manifested as hyponatremia and hyperkalemia (In mild forms of salt-wasting adrenal hyperplasia, salt wasting may not become apparent until an illness stresses the child). Here hyperkalaemia inspite of vomiting is indicating the disease].

The key is C. DiGeorge syndrome. [Points in favour'

i) Early age of onset

ii) abnormal facies

iii) absent thymic shadow on Chest X-ray

iii) history of recurrent infection [Infections are common in children due to problems with the immune system's T-cell-mediated response that in some patients is due to an absent or hypoplastic thymus].

In newborn can be recognized by convulsions from hypocalcaemia due to malfunctioning parathyroid glands and low levels of parathyroid hormones].

Ans. The key is A. Down’s syndrome. [Double bubble sign indicates duodenal atresia which is a common association with Down’s syndrome].

Ans. The key is A. Osteogenesis imperfecta. [Osteogenesis imperfecta (OI), also known as brittle bone disease, is a group of genetic disorders that mainly affect the bones.

It results in bones that break easily.

OI may have joint hyperlaxity; muscle weakness; chronic, unremitting bone pain; and skull deformities (eg, posterior flattening) due to bone fragility during infancy.

Limb shortening and progressive deformities can occur, and patients have a triangular face with frontal and temporal bossing; malocclusion is common. The sclera have variable hues commonly blue]

Ans. The key is A. cystic fibrosis. [CF involves in production of sweat, respiratory mucous, digestive fluid, and mucous. These secretions become thicker than normal predisposing to lung and GI infections since birth].

The key is C. Alpha 1 antitrypsin deficiency. [Unexplained liver disease with respiratory symptoms are very suggestive of AATD].

Ans. The key is C. Prader Willi syndrome. [Prader-Willi syndrome rare congenital disorder characterized by learning difficulties, growth abnormalities, and obsessive eating, caused especially by the absence of certain genes normally present on the copy of chromosome 15 inherited from the father].

Ans. The key is D. Depends on the genetic makeup of the partner. [Depends on the make-up of the partner, ideally it's 1:2 since it's autosomal dominant with complete penetrance but if the patient's spouse also has neurofibromatosis, which raises it to at least 75% with a possible 100%].

Ans. The key is B. Liver.

Diagnosis is hemochromatosis. Hemochromatosis is an abnormal accumulation of iron in parenchymal organs, leading to organ toxicity.

It is the most common autosomal recessive genetic disorder and the most common cause of severe iron overload leading to hepatomegaly, liver cirrhosis and liver cancer, hyperpigmentation, diabetes mellitus, arthropathy, cardiomyopathy etc.

The key is C. Hemochromatosis. [In hemochromatosis distribution pattern of iron in liver biopsy by pearl’s stain is more prominent iron granules in periportal hepatocytes and relative sparing of kupffer cells and decreased intensity near the central vein.

By contrast, iron overload in hemosiderosis causes to accumulation of iron granules predominantly in Kupfer cells and more in the central area rather than peripheral hepatocytes. In the given case there are large amount of iron pigment in hepatocytes which is diagnostic of hemochromatosis].

The key is C. Turner’s syndrome. [Down’s syndrome and Fragile X syndrome don’t have primary amenorrhea. Klinefelter syndrome patients are tall males. So the likely diagnosis is Turner’s syndrome].

Ans. The key is D. Hepatoma. [Increased skin pigmentation, features of chronic liver disease (spider angioma), Cardiomyopathy (cardiomegaly, S3 gallop), and Enlarged liver are suggestive of Haemochromatosis. If cirrhosis, 22–30% get hepatocellular cancer].

The key is A. Galactosemia. [Galactosemia is a family of genetic disorders that result from compromised ability to metabolize the sugar galactose; the term “galactosemia” literally means too much galactose in the blood. Biliary atresia causes obstructive pictures where stools are pale and the urine becomes dark.

Hemolytic disorders like G6PD or spherocytosis cause the appearance of jaundice in 1st 24 hours. In breastmilk jaundice, jaundice develops in 2nd week. Also, congenital viral infection (TORCH) occurs in 1st 24 hours. Here there is failure to thrive also. So likely cause in the presented case is Galactosemia].

Ans. The key is D. Karyotyping. [The likely diagnosis is Klinefelter’s syndrome for which Karyotyping should be done to make the diagnosis established].

C. Pre-implantation genetic diagnosis. [Patient is not yet pregnant but planning for pregnancy. The earliest possible diagnostic test for cystic fibrosis is Pre-implantation genetic diagnosis.

Preimplantation genetic diagnosis (PGD) is a procedure used prior to implantation to help identify genetic defects within embryos created through in vitro fertilization to prevent certain diseases or disorders from being passed on to the child].

The key is D. Alpha 1 antitrypsin deficiency. [In those with unexplained liver disease with or without respiratory symptoms should be evaluated for AATD].

Ans. The key is C. 1:4. [Cystic fibrosis is an autosomal recessive disease. If both parents are carrier there is a 1:4 chance of risk of occurrence of the disease for each child].

Ans. The key is B. 1:2. [As the parents have a child with cystic fibrosis and they are healthy both of them are carriers. It is an autosomal recessive disease where if both parents are carriers mode of inheritance is as follows: Chance of being a healthy child 1:4, Chance of being diseased 1:4, and chance of being a carrier 1:2].

The key is A. There is a 1:4 chance that your future child will have this disease. [It is an autosomal recessive disease. As one child is affected both parents are carriers. So in this case next child will be normal in 1:4 cases, carrier in 1:2 cases and diseased in 1:4 cases].

Ans. The key is the A. Sweat test. [The sweat test measures the concentration of chloride that is excreted in sweat. It is used to screen for cystic fibrosis (CF). Due to defective chloride channels, the concentration of chloride in sweat is elevated in individuals with cystic fibrosis].

Ans. The key is D. AD [Hereditary hemorrhagic telangiectasia has an autosomal dominant mode of inheritance].

The key is C. Inherited as sex-linked recessive condition.

Ans. The key is C. Duchenne muscular dystrophy. [The child having difficulty with walking, running, jumping, and climbing stairs. Walking may look different with a 'waddling' type of walk.

The boy may be late in starting to walk (although many children without DMD also walk late). When you pick the child up, you may feel as if he 'slips through your hands', due to looseness of the muscles around the shoulder.

The calf muscles may look bulky, although they are not strong. As he gets older, the child may use his hands to help him get up, looking as if he is 'climbing up his legs'. This is called 'Gower's sign'].

The key is A. AD inheritance with anticipation. [Patient is suffering from Huntington's disease and that is autosomal dominant with anticipation which means a genetic disorder is passed on to the next generation, the symptoms of the genetic disorder become apparent at an earlier age with each generation].

The key is A. Gaucher disease

Ans. The key is B. 1:2. [Probable diagnosis is neurofibromatosis type 2. The mode of inheritance is autosomal dominant. So the inheritance ratio is 1:2].